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BioMed Research International
Volume 2015, Article ID 198418, 10 pages
http://dx.doi.org/10.1155/2015/198418
Research Article

Intratracheal Bleomycin Aerosolization: The Best Route of Administration for a Scalable and Homogeneous Pulmonary Fibrosis Rat Model?

1Laboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, Belgium
2Department of Pneumology, Erasme Hospital, 1070 Brussels, Belgium
3Laboratory of Histology, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, Belgium

Received 6 October 2014; Accepted 9 January 2015

Academic Editor: Oreste Gualillo

Copyright © 2015 Alexandre Robbe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic disease with a poor prognosis and is characterized by the accumulation of fibrotic tissue in lungs resulting from a dysfunction in the healing process. In humans, the pathological process is patchy and temporally heterogeneous and the exact mechanisms remain poorly understood. Different animal models were thus developed. Among these, intratracheal administration of bleomycin (BML) is one of the most frequently used methods to induce lung fibrosis in rodents. In the present study, we first characterized histologically the time-course of lung alteration in rats submitted to BLM instillation. Heterogeneous damages were observed among lungs, consisting in an inflammatory phase at early time-points. It was followed by a transition to a fibrotic state characterized by an increased myofibroblast number and collagen accumulation. We then compared instillation and aerosolization routes of BLM administration. The fibrotic process was studied in each pulmonary lobe using a modified Ashcroft scale. The two quantification methods were confronted and the interobserver variability evaluated. Both methods induced fibrosis development as demonstrated by a similar progression of the highest modified Ashcroft score. However, we highlighted that aerosolization allows a more homogeneous distribution of lesions among lungs, with a persistence of higher grade damages upon time.